title: Sudden cardiac death: still more questions than answers.
abstract: Sudden cardiac death is the leading cause of death in industrialized countries. It is most frequently due to ventricular tachyarrhythmias occurring in the presence of coronary heart disease, but mechanisms linking sudden death to coronary atherosclerosis are still unclear. In autopsy studies of sudden death patients, the incidence of acute thrombotic coronary occlusions has varied between 4 and 74%. In over 600 consecutive patients with implantable cardioverter-defibrillators, we observed that appropriate shocks for electrogram-verified ventricular tachyarrhythmias was only very rarely followed by signs of acute myocardial infarction (< 3% of cases), not supporting the coronary occlusion theory of fatal arrhythmias. Cellular hypertrophy compensating for cell loss due to ischemia, intraventricular hypertension, cardiomyopathy, and myocarditis might play a role in arrhythmogenesis as evidenced by the fact that experimental induction and regression of hypertrophy are paralleled by changes in the inducibility of ventricular tachyarrhythmias. Atherogenic hyperlipidemias are associated with a systemic inflammatory response manifested by leukocytosis (lymphocytosis) and complex upregulations of proinflammatory-prothrombotic mediators, such as platelet-activating factor, cytokines, and hemostasis factors. The diurnal regulation of these mediators parallels circadian rhythms of coronary morbidity and mortality. Some upregulated mediators have been shown to exert direct arrhythmogenic effects. The potential contribution of hyperlipidemia-associated inflammatory factors to arrhythmogenesis is important, because it opens new molecular targets for antiarrhythmic drug design.
authors.affiliation: Texas Arrhythmia Institute, Houston, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Henry
authors.forename: A
authors.initials: A
authors.lastname: Pacifico
mesh_terms: D006332:Cardiomegaly / Q000150:complications; D002940:Circadian Rhythm; D003328:Coronary Thrombosis / Q000150:complications; D016757:Death, Sudden, Cardiac / Q000209:etiology; D006801:Humans; D009205:Myocarditis / Q000150:complications; D014693:Ventricular Fibrillation / Q000150:complications / Q000188:drug therapy